Abstract
Circadian dysfunction is a common non-motor symptom in Parkinson’s disease (PD). The potential influence of aggravated α-synuclein (SNCA) on circadian disruption remains unclear. SNCAA53T-overexpressing transgenic mice (SNCAA53T mice) and wild-type (WT) littermates were used in this study. The energy metabolism cage test showed differences in 24-h activity pattern between SNCAA53T and WT mice. When compared with the age-matched littermates, brain and muscle ARNT-like 1 (BMAL1) was downregulated in SNCAA53T mice. BMAL1 was downregulated in PC12 cells overexpressing SNCA. Degradation of BMAL1 protein remained unchanged after overexpression of SNCA, while its mRNA level decreased. miRNA (miR)-155 was upregulated by overexpression of SNCA, and downregulation of BMAL1 was partially reversed by transfection with miR-155 inhibitor. Our findings demonstrated that overexpression of SNCA induced biorhythm disruption and downregulated BMAL1 expression through decreasing stability of BMAL1 mRNA via miR-155.
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Funding
This work was supported by the National Natural Science Foundation of China (81801253), Natural Science Foundation of Jiangsu Province (BK20180214), the Seventh Batch of GuSu District Health Talent Training Project (GSWS2020076).
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(I) Conception and design, Wang YL and Dong WL; (II) administrative support, none; (III) provision of study materials or patients, none; (IV) experiment conducting, Liu JY and Xue J; (V) data analysis and interpretation, Liu JY and Wang F; (VI) manuscript writing, all authors; and (VII) final approval of manuscript, all authors.
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Liu, JY., Xue, J., Wang, F. et al. α-Synuclein-Induced Destabilized BMAL1 mRNA Leads to Circadian Rhythm Disruption in Parkinson’s Disease. Neurotox Res 41, 177–186 (2023). https://doi.org/10.1007/s12640-022-00633-0
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DOI: https://doi.org/10.1007/s12640-022-00633-0